The long term objective of this work is to create long-lived, self-healing materials for use in load-bearing biomaterials applications, particularly orthopedic prostheses such as artificial hips and articular cartilage. The strategy employed is to follow Nature's example of hierarchal material design, where the hierarchy is organized through well-defined, specific noncovalent interactions. The underlying hypothesis is that the optimal design of reversibly self-polymerizing monomers will ultimately yield materials that solve one of the important design criteria for ideal biomaterial implants, namely resistance to fatigue-induced fracture and wear. The molecular mechanisms of fatigue support the validity of that hypothesis. Specifically, this research investigates molecular assembly and mechanical properties between interfaces, which is directly relevant to fatigue-the primary mechanism of mechanical failure in many biomaterials, including hip prostheses. The reversibly associating monomers described in this proposal comprise two families. The first family of molecules is based on oligonucleotide duplex formation, and the second is based on reversible metal-ligand association. Both families are compatible with aqueous, ionic environments. Each is amenable to a wide range of structural variations. Importantly, atomic force microscopy reveals behaviors that are directly relevant to fatigue resistance: surface-to-surface bridging and main chain self-repair. These behaviors are observed with concomitant tribological and mechanical properties that lend themselves to biomaterials applications. The significance of this project stems from the ability to combine and expand the force microscopy experiments with the modularity afforded by the two families of compounds. In so doing, this work will elucidate the relationship between the structure and properties of individual molecules and the nano-, meso- and macroscale properties of their assemblies. The principles learnt from these studies will guide the synthesis of a first-generation self-healing biomaterial in the latter stages of the project.